Glue for cartilage repair

ABSTRACT

The invention is directed toward a sterile cartilage defect implant material comprising milled lyophilized allograft cartilage pieces ranging from 0.01 mm to 1.0 mm in size in a bioabsorbable carrier taken from a group consisting of sodium hyaluronate, hyaluronic acid and its derivatives, gelatin, collagen, chitosan, alginate, buffered PBS, Dextran or polymers with allogenic chondrocytes or bone marrow cells in an amount exceeding the natural occurrence of same in hyaline cartilage and adding a cell growth additive.

RELATED APPLICATIONS

There is no related application.

1. Field of Invention

The present invention is generally directed toward an implant and ismore specifically directed toward a paste or gel implant material for acartilage defect.

2. Background of the Invention

Articular cartilage injury and degeneration present medical problems tothe general population which are addressed by orthopedic surgeons. Everyyear in the United States, over 500,000 arthroplastic or joint repairprocedures are performed. These include approximately 125,000 total hipand 150,000 total knee arthroplastics and over 41,000 open arthroscopicprocedures to repair cartilaginous defects of the knee.

In the knee joint, the articular cartilage tissue forms a lining whichfaces the joint cavity on one side and is linked to the subchondral boneplate by a narrow layer of calcified cartilage tissue on the other.Articular cartilage (hyaline cartilage) consists primarily ofextracellular matrix with a sparse population of chondrocytesdistributed throughout the tissue. Articular cartilage is composed ofchondrocytes, type II collagen fibril network, proteoglycans and water.Active chondrocytes are unique in that they have a relatively lowturnover rate and are sparsely distributed within the surroundingmatrix. The collagens give the tissue its form and tensile strength andthe interaction of proteoglycans with water give the tissue itsstiffniess to compression, resilience and durability. The hyalinecartilage provides a low friction bearing surface over the bony parts ofthe joint. If the lining becomes worn or damaged resulting in lesions,joint movement may be painful or severely restricted. Whereas damagedbone typically can regenerate successfully, hyaline cartilageregeneration is quite limited because of it's limited regenerative andreparative abilities.

Articular cartilage lesions generally do not heal, or heal onlypartially under certain biological conditions due to the lack of nerves,blood vessels and a lymphatic system. The limited reparativecapabilities of hyaline cartilage usually results in the generation ofrepair tissue that lacks the structure and biomechanical properties ofnormal cartilage. Generally, the healing of the defect results in afibrocartilaginous repair tissue that lacks the structure and biomedicalproperties of hyaline cartilage and degrades over the course of time.Articular cartilage lesions are frequently associated with disabilityand with symptoms such as joint pain, locking phenomena and reduced ordisturbed function. These lesions are difficult to treat because of thedistinctive structure and function of hyaline cartilage. Such lesionsare believed to progress to severe forms of osteoarthritis.Osteoarthritis is the leading cause of disability and impairment inmiddle-aged and older individuals, entailing significant economic,social and psychological costs. Each year, osteoarthritis accounts foras many as 39 million physician visits and more than 500,000hospitalizations. By the year 2020, arthritis is expected to affectalmost 60 million persons in the United States and to limit the activityof 11.6 million persons.

There are many current therapeutic methods being used. None of thesetherapies has resulted in the successful regeneration of hyaline-liketissue that withstands normal joint loading and activity over prolongedperiods. Currently, the techniques most widely utilized clinically forcartilage defects and degeneration are not articular cartilagesubstitution procedures, but rather lavage, arthroscopic debridement,and repair stimulation. The direct transplantation of cells or tissueinto a defect and the replacement of the defect with biologic orsynthetic substitutions presently accounts for only a small percentageof surgical interventions. The optimum surgical goal is to replace thedefects with cartilage-like substitutes so as to provide pain relief,reduce effusions and inflammation, restore function, reduce disabilityand postpone or alleviate the need for prosthetic replacement.

Lavage and arthroscopic debridement involve irrigation of the joint withsolutions of sodium chloride, Ringer or Ringer and lactate. Thetemporary pain relief is believed to result from removing degenerativecartilage debris, proteolytic enzymes and inflammatory mediators. Thesetechniques provide temporary pain relief, but have little or nopotential for further healing.

Repair stimulation is conducted by means of drilling, abrasionarthroplasty or microfracture. Penetration into the subchondral boneinduces bleeding and fibrin clot formation which promotes initialrepair, however, the tissue formed is fibrous in nature and not durable.Pain relief is temporary as the tissue exhibits degeneration, loss ofresilience, stiffness and wear characteristics over time.

The periosteum and perichondrium have been shown to contain mesenchymalprogenitor cells capable of differentiation and proliferation. They havebeen used as grafts in both animal and human models to repair articulardefects. Few patients over 40 years of age have obtained good clinicalresults, which most likely reflects the decreasing population ofosteochondral progenitor cells with increasing age. There have also beenproblems with adhesion and stability of the grafts, which result intheir displacement or loss from the repair site.

Transplantation of cells grown in culture provides another method ofintroducing a new cell population into chondral and osteochondraldefects. Carticel® is a commercial process to culture a patient's owncartilage cells for use in the repair of cartilage defects in thefemoral condyle marketed by Genzyme Biosurgery in the United States andEurope. The procedure uses arthroscopy to take a biopsy from a healthy,less loaded area of articular cartilage. Enzymatic digestion of theharvested tissue releases the cells that are sent to a laboratory wherethey are grown for a period ranging from 2–5 weeks. Once cultivated, thecells are injected during a more open and extensive knee procedure intoareas of defective cartilage where it is hoped that they will facilitatethe repair of damaged tissue. An autologous periosteal flap with cambiumlayer is used to seal the transplanted cells in place and act as amechanical barrier. Fibrin glue is used to seal the edges of the flap.This technique preserves the subchondral bone plate and has reported ahigh success rate. Proponents of this procedure report that it producessatisfactory results, including the ability to return to demandingphysical activities, in more than 90% of patients and that biopsyspecimens of the tissue in the graft sites show hyaline-like cartilagerepair. More work is needed to assess the function and durability of thenew tissue and determine whether it improves joint function and delaysor prevents joint degeneration. As with the perichondrial graft,patient/donor age may compromise the success of this procedure aschondrocyte population decreases with increasing age. Disadvantages tothis procedure include the need for two separate surgical procedures,potential damage to surrounding cartilage when the periosteal patch issutured in place, the requirement of demanding microsurgical techniques,and the expensive cost of the procedure which is currently not coveredby insurance.

Osteochondral transplantation or mosaicplasty involves excising allinjured or unstable tissue from the articular defect and creatingcylindrical holes in the base of the defect and underlying bone. Theseholes are filled with autologous cylindrical plugs of healthy cartilageand bone in a mosaic fashion. The osteochondral plugs are harvested froma lower weight-bearing area of lesser importance in the same joint. Thistechnique, shown in Prior Art FIG. 2, can be performed as arthroscopicor open procedures. Reports of results of osteochondral plug autograftsin a small number of patients indicate that they decrease pain andimprove joint function, however, long-term results have not beenreported. Factors that can compromise the results include donor sitemorbidity, effects of joint incongruity on the opposing surface of thedonor site, damage to the chondrocytes at the articular margins of thedonor and recipient sites during preparation and implantation, andcollapse or settling of the graft over time. The limited availability ofsites for harvest of osteochondral autografts restricts the use of thisapproach to treatment of relatively small articular defects and thehealing of the chondral portion of the autograft to the adjacentarticular cartilage remains a concern.

Transplantation of large allografts of bone and overlying articularcartilage is another treatment option that involves a greater area thanis suitable for autologous cylindrical plugs, as well as for anon-contained defect. The advantages of osteochondral allografts are thepotential to restore the anatomic contour of the joint, lack ofmorbidity related to graft harvesting, greater availability thanautografts and the ability to prepare allografts in any size toreconstruct large defects. Clinical experience with fresh and frozenosteochondral allografts shows that these grafts can decrease jointpain, and that the osseous portion of an allograft can heal to the hostbone and the chondral portion can function as an articular surface.Drawbacks associated with this methodology in the clinical situationinclude the scarcity of fresh donor material and problems connected withthe handling and storage of frozen tissue. Fresh allografts carry therisk of immune response or disease transmission. MusculoskeletalTransplant Foundation (MTF) has preserved fresh allografts in a mediathat maintains a cell viability of 50% for 35 days for use as implants.Frozen allografts lack cell viability and have shown a decreased amountof proteoglycan content which contribute to deterioration of the tissue.

A number of patents in the prior art show the use of bone putty, pastesor gels to fill bone defects. U.S. Pat. No. 5,290,558 issued Mar. 1,1994 discloses a flowable demineralized bone powder composition using anosteogenic bone powder with large particle size ranging from about 0.1to about 1.2 cm. mixed with a low molecular weight polyhydroxy compoundpossessing from 2 to about 18 carbons including a number of classes ofdifferent compounds such as monosaccharides, disaccharides, waterdispersible oligosaccharides and polysaccharides.

A bone gel is disclosed in the U.S. Pat. No. 5,073,373 issued Dec. 17,1991. Bone lamellae in the shape of threads or filaments retaining lowmolecular weight glycerol carrier are disclosed in U.S. Pat. Nos.5,314,476 issued May 24, 1994 and 5,507,813 issued Apr. 16, 1996 and thetissue forms described in these patents are known commercially as theGRAFTON® Putty and Flex, respectively.

U.S. Pat. No. 5,356,629 issued Oct. 18, 1994 discloses making a rigidgel in the nature of a bone cement to fill defects in bone by mixingbiocompatible particles, preferably polymethylmethacrylate coated withpolyhydroxyethylmethacrylate in a matrix selected from a group whichlists hyaluronic acid to obtain a molded semi-solid mass which can besuitably worked for implantation into bone. The hyaluronic acid can alsobe utilized in monomeric form or in polymeric form preferably having amolecular weight not greater than about one million Daltons. It is notedthat the nonbioabsorbable material which can be used to form thebiocompatible particles can be derived from xenograft bone, homologousbone, autogenous bone as well as other materials. The bioactivesubstance can also be an osteogenic agent such as demineralized bonepowder, morselized cancellous bone, aspirated bone marrow and otherautogenous bone sources. The average size of the particles employed ispreferably about 0.1 to about 3.0 mm, more preferably about 0.2 to about1.5 mm, and most preferably about 0.3 to about 1.0 mm. It isinferentially mentioned but not taught that particles having averagesizes of about 7,000 to 8,000 microns, or even as small as about 100 to700 microns can be used.

U.S. Pat. No. 4,172,128 issued Oct. 23, 1979 discloses a demineralizedbone material mixed with a carrier to reconstruct tooth or bone materialby adding a mucopolysaccharide to a mineralized bone colloidal material.The composition is formed from a demineralized coarsely ground bonematerial, which may be derived from human bones and teeth, dissolved ina solvent forming a colloidal solution to which is added aphysiologically inert polyhydroxy compound such as mucopolysaccharide orpolyuronic acid in an amount which causes orientation when hydrogen ionsor polyvalent metal ions are added to form a gel. The gel will beflowable at elevated temperatures above 35° C. and will solidify whenbrought down to body temperature. Example 25 of the patent notes thatmucopolysaccharides produce pronounced ionotropic effects and thathyaluronic acid is particularly responsible for spatial cross-linking.

U.S. Pat. No. 6,030,635 issued Feb. 29, 2000 and U.S. Pat. No. 6,437,018issued Aug. 20, 2002 are directed toward a malleable bone putty and aflowable gel composition for application to a bone defect site topromote new bone growth at the site which utilize a new bone growthinducing compound of demineralized lyophilized allograft bone powder.The bone powder has a particle size ranging from about 100 to about 850microns and is mixed in a high molecular weight hydrogel carrier whichcontains a sodium phosphate saline buffer.

The use of implants for cartilage defects is much more limited. Asidefrom the fresh allograft implants and autologous implants, U.S. Pat. No.6,110,209 issued Nov. 5, 1998 shows the use an autologous articularcartilage cancerous bone paste to fill arthritic defects. The surgicaltechnique is arthroscopic and includes debriding (shaving away loose orfragmented articular cartilage), followed by morselizing the base of thearthritic defect with an awl until bleeding occurs. An osteochondralgraft is then harvested from the inner rim of the intercondylar notchusing a trephine. The graft is then morselized in a bone graft crusher,mixing the articular cartilage with the cancellous bone. The paste isthen pushed into the defect and secured by the adhesive properties ofthe bleeding bone. The paste can also be mixed with a cartilagestimulating factor, a plurality of cells, or a biological glue. Allpatients are kept non-weight bearing for four weeks and used acontinuous passive motion machine for six hours each night. Histologicappearance of the biopsies have mainly shown a mixture of fibrocartilagewith hyaline cartilage. Concerns associated with this method are harvestsite morbidity and availability, similar to the mosaicplasty method.

SUMMARY OF THE INVENTION

A cartilage implant material in paste or gel form for repairingarticular cartilage defects is composed of milled allograft cartilagepieces in a bioabsorbable carrier. Autologous chondrocyte in an amountexceeding the number naturally occurring in hyaline cartilage for amature adult between 20 and 55 years of age may also be applied to thematrix. Additives may be applied to the mixture in order to increasechondrocyte migration and proliferation. The implant material cansupport the addition of a variety of chondrogenic stimulating factorsincluding, but not limited to growth factors (FGF-2, FGF-5, IGF-1,TGF-β, BMP-2, BMP-7, PDGF, VEGF), human allogenic or autologouschondrocytes, human allogenic or autologous bone marrow cells, stemcells, demineralized bone matrix, insulin, insulin-like growth factor-1,transforming growth factor-B, interleukin-1 receptor antagonist,hepatocyte growth factor, platelet-derived growth factor, Indianhedgehog and parathyroid hormone-related peptide or bioactive glue.

The implant material is placed in the lesion area and may be sealed witha periosteum cap.

It is an object of the invention to provide an allograft implantmaterial for joints which provides pain relief, restores normal functionand will postpone or alleviate the need for prosthetic replacement.

It is also an object of the invention to provide a cartilage repairimplant material which is easily placed in a defect area by the surgeonusing an arthroscopic, minimally invasive technique.

It is further an object of the invention to provide an allograft implantmaterial procedure which is applicable for both partial and fullthickness lesions.

It is yet another object of the invention to provide an allograftimplant material which facilitates growth of hyaline cartilage.

It is an additional object of the invention to provide implant paste andgel material formulations that satisfy surgical requirements and aremade from donated human available allograft tissue, some of which wouldotherwise be considered waste and thrown away.

These and other objects, advantages, and novel features of the presentinvention will become apparent when considered with the teachingscontained in the detailed disclosure along with the accompanyingdrawings.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 shows the anatomy of a knee joint with a lesion;

FIG. 2 shows a schematic mosaicplasty as known in the prior art; and

FIG. 3 shows a schematic perspective view of cartilage defect materialplaced in a defect site with an exploded periosteum cap.

DESCRIPTION OF THE INVENTION

The terms “tissue” is used in the general sense herein to mean anytransplantable or implantable tissue, the survivability of which isimproved by the methods described herein upon implantation. Inparticular, the overall durability and longevity of the implant areimproved, and host-immune system mediated responses, are substantiallyeliminated.

The terms “transplant” and “implant” are used interchangably to refer totissue, material or cells (xenogeneic or allogeneic) which may beintroduced into the body of a patient to replace or supplement thestructure or function of the endogenous tissue.

The terms “autologous” and “autograft” refer to tissue or cells whichoriginate with or are derived from the recipient, whereas the terms“allogeneic” and “allograft” refer to cells and tissue which originatewith or are derived from a donor of the same species as the recipient.The terms “xenogeneic” and “xenograft” refer to cells or tissue whichoriginates with or is derived from a species other than that of therecipient.

The term “gel” refers to a mixture of minced or milled pretreatedallograft cartilage in a biocomposite carrier having a viscosity whichis less than and is less rigid than a mixture of minced or milledpretreated allograft cartilage in a biocompatible carrier referred to bythe terms “putty” or “paste” and contains less cartilage by weight thanputty or paste.

The present invention is directed towards a cartilage repair materialand method of treatment. The preferred embodiment and best mode of theinvention is shown in FIG. 3. In the production of the invention,allograft hyaline cartilage is lyophilized reducing its water contentand milled for ease in application.

After washes with sterile de-ionized (DI) water, the cartilage materialwas frozen at −20° to −100° C. preferably −70° C. and lyophilized toreduce the water content within the range of about 0.1% to about 8.0%.The cartilage is frozen with liquid nitrogen and ground into particles.

A lesion or defect is removed by cutting a bore 50 or trimming a lesionin the implant area 100 and filling the bore 50 or lesion area with amilled cartilage mixture 20 of paste or gel consisting together with abiological carrier such as hyaluronic acid and its derivatives, gelatin,collagen, chitosan, alginate, buffered PBS, Dextran, or polymers and oneor more additives namely chondrogenic stimulating factors including, butnot limited to growth factors (FGF-2, FGF-5, IGF-1, TGF-β, BMP-2, BMP-7,PDGF, VEGF), human allogenic or autologous chondrocytes, human allogeniccells, human allogenic or autologous bone marrow cells, human allogenicor autologous stem cells, demineralized bone matrix, insulin,insulin-like growth factor-1, interleukin-1 receptor antagonist,hepatocyte growth factor, platelet-derived growth factor, Indianhedgehog and parathyroid hormone-related peptide.

Suitable organic glue material can be used to keep the viscous cartilagemixture 20 fixed in place in the implant area or to affix a periostealcap 30 in place over the surrounding hyaline cartilage area 100.Suitable organic glue material can be found commercially, such as forexample; TISSEEL® or TISSUCOL.®) (fibrin based adhesive; Immuno AG,Austria), Adhesive Protein (Sigma Chemical, USA), and Dow CorningMedical Adhesive B (Dow Corning, USA).

EXAMPLE 1

A matrix of minced cartilage putty consisting of minced or milledallograft articular cartilage which has been lyophilized so that itswater content ranges from 0.1% to 8.0% with a cartilage content rangingfrom 25% to 50% by weight is mixed with a carrier of sodium hyaluronatesolution (HA) (molecular weight ranging from 7.0×10⁵ to 1.2×10⁶) or anyother bioabsorbable carrier such as hyaluronic acid and its derivatives,gelatin, collagen, chitosan, alginate, buffered PBS, Dextran, orpolymers, the carrier ranging from 75% to 50% by weight. The cartilageis milled to a size ranging from 0.01 mm to 1 mm. In gel form, theminced cartilage which has been lyophilized so that its water contentranges from 0.1% to 8.0% ranging from 15% to 30% by weight and thecarrier ranges from 85% to 70% by weight. The particle size of thecartilage when milled is less than or equal to 1 mm dry in thepreviously stated range. The cartilage pieces can be processed tovarying particle sizes and the HA or other carrier can have differentviscosities depending on the desired consistency of the putty or paste.This cartilage matrix can be deposited into the cartilage defectarthroscopically and fit into the defect where it is held in place byit's own viscosity, mixed with fibrin glue or covered with a periostealor perichondrial flap, then sealed with biological glue. As with thefirst two matrices, this matrix can support the previously mentionedchondrogenic factors.

EXAMPLE 2

A matrix of minced cartilage putty consisting of minced or milledallograft cartilage which has been lyophilized so that its water contentranges from 0.1% to 8.0% ranging from 25% to 50% by weight is mixed witha carrier of sodium hyaluronate solution (HA) (7.0×10⁵ to 1.2×10⁶) orany other bioabsorbable carrier such as hyaluronic acid and itsderivatives, gelatin, collagen, chitosan, alginate, buffered PBS,Dextran, or polymers ranging from 75% to 50% by weight. In a gel form,the minced cartilage which has been lyophilized so that its watercontent ranges from 0.01% to 8.0% ranging from 15% to 30% by weight andthe carrier ranges from 85% to 70% by weight. The particle size of thecartilage is less than or equal to 1 mm dry ranging from 0.01 mm to 1mm. The cartilage pieces can be processed to varying particle sizes andthe HA or carrier can have different viscosities depending on thedesired consistency of the putty or paste. Autologous or allogenic cellswhich have been grown outside the patient are inserted by syringe intothe matrix before, during or after deposit of the cartilage matrix intothe defect area. Such cells include allogenic or autologous bone marrowcells, stem cells and chondrocyte cells. The cellular density of thecells preferably ranges from about 1×10⁸ to 5×10⁸ or from about 100million to about 500 million cells per cc of putty or gel mixture. Thiscomposite material can be injected into the cartilage defectarthroscopically and fit into the defect where it is held in place byit's own viscosity, or covered with a periosteal or perichondrial flap,then sealed with biological glue. As with the first matrix, this matrixcan support the previously mentioned chondrogenic factors.

The operation of placing the cartilage composition in a cartilagedefect, comprises (a) cutting a patient's tissue at a site of acartilage defect to remove the diseased area of cartilage; (b) placing amixture of milled allograft cartilage in a bioabsorbable carrier in thedefect area; and (c) placing a periosteal cover over the mixture of theinserted milled allograft cartilage in a bioabsorbable carrier tocontain the mixture in the defect area for a predetermined period oftime to promote cartilage growth at the defect site. Alternate stepsinclude the addition of growth factors, chondrocytes, bone marrow cellsand stem cells.

The principles, preferred embodiments and modes of operation of thepresent invention have been described in the foregoing specification.However, the invention should not be construed as limited to theparticular embodiments which have been described above. Instead, theembodiments described here should be regarded as illustrative ratherthan restrictive.

1. A sterile allograft cartilage defect implant material for use inhuman beings comprising milled allograft cartilage pieces sized lessthan 1 mm and lyophilized so that their water content ranges from about0.1% to about 8.0% in a bioabsorbable carrier.
 2. A sterile allograftcartilage defect implant material as claimed in claim 1 wherein saidmilled cartilage ranges from about 25% to about 50% by weight and saidcarrier ranges from about 75% to about 50% by weight.
 3. A sterileallograft cartilage defect implant material as claimed in claim 1wherein said milled cartilage ranges from about 15% to about 30% byweight with the carrier ranging from about 85% to about 70% by weight.4. A sterile allograft cartilage defect implant material as claimed inclaim 1 wherein said carrier is sodium hyaluronate and its derivatives.5. A sterile allograft cartilage defect implant material as claimed inclaim 1 wherein said implant material includes a protein glue.
 6. Asterile allograft cartilage defect implant material as claimed in claim1 wherein said implant material includes the addition of autologouschondrocytes to achieve a concentration exceeding the concentration ofchondrocytes naturally occurring in the patient.
 7. A sterile allograftcartilage defect implant material as claimed in claim 1 wherein saidmilled cartilage is hyaline cartilage.
 8. A sterile allograft cartilagedefect implant material as claimed in claim 1 wherein said milledcartilage is fibrosus cartilage.
 9. A sterile allograft cartilage defectimplant material as claimed in claim 1 wherein said milled cartilage ishyaline and fibrosus cartilage.
 10. A sterile allograft cartilage defectimplant material claimed in claim 1 including an additive to saidimplant material consisting of one or more of a group consisting ofgrowth factors, human allogenic cells, human allogenic bone marrowcells, human autologous bone marrow cells, human allogenic stem cells,human autologous stem cells, human demineralized bone matrix, andinsulin.
 11. A sterile cartilage repair material as claimed in claim 10wherein said growth factors are one or more of a group consisting ofFGF-2, FGF-5, IGF-1, TGF-β, BMP-2, BMP-7, PDGF, VEGF.
 12. A sterileallograft cartilage defect implant material as claimed in claim 1wherein said carrier comprises one or more bioabsorbable carriers takenfrom a group consisting of sodium hyaluronate, hyaluronic acid and itsderivatives, gelatin, collagen, chitosan, alginate, buffered PBS,Dextran or polymers.
 13. A sterile cartilage defect implant materialcomprising milled allograft articular cartilage pieces ranging from 0.01mm to 1.0 mm in size in a bioabsorbable carrier taken from a groupconsisting of sodium hyaluronate, gelatin, collagen, chitosan, alginate,buffered PBS, Dextran or polymers and allogenic chondrocytes in anamount exceeding the natural occurrence of same in articular cartilage.14. A sterile cartilage defect implant material as claimed in claim 13wherein said allograft articular cartilage is hyaline cartilage.
 15. Asterile allograft cartilage defect implant material as claimed in claim13 wherein said milled cartilage is fibrous cartilage.
 16. A sterileallograft cartilage defect implant material as claimed in claim 13wherein said milled cartilage is hyaline and fibrous cartilage.
 17. Asterile cartilage repair material as claimed in claim 13 wherein saidimplant material includes an additive consisting of one or more of agroup consisting of growth factors, human allogenic cells, humanallogenic bone marrow cells, human autologous bone marrow cells, humanallogenic stem cells, human autologous stem cells, demineralized bonematrix, and insulin.
 18. A sterile cartilage repair material as claimedin claim 17 wherein said growth factors are one or more of a groupconsisting of FGF-2, FGF-5, IGF-1, TGF-β, BMP-2, BMP-7, PDGF, VEGF. 19.A sterile cartilage defect implant material as claimed in claim 13wherein said milled cartilage ranges from about 25% to about 50% byweight and said carrier ranges from about 75% to about 50% by weight.20. A sterile cartilage defect implant material as claimed in claim 13wherein said milled cartilage ranges from about 15% to about 30% byweight with the carrier ranging from about 85% to about 70% by weight.21. A sterile cartilage defect implant material comprising lyophilizedmilled allograft articular cartilage pieces ranging from 0.01 mm to 1.0mm in size in a bioabsorbable carrier taken from a group consisting ofsodium hyaluronate, hyaluronic acid and its derivatives, gelatin,collagen, chitosan, alginate, buffered PBS, Dextran or polymers andautologous bone marrow cells in an amount exceeding the naturaloccurrence of same in a patient being treated.
 22. A sterile cartilagedefect repair material as claimed in claim 21 including an additive insaid implant material which consists of one or more of a groupconsisting of growth factors, human allogenic cells, autologouschondrocytes, demineralized bone matrix, and insulin.
 23. A sterilecartilage repair material as claimed in claim 22 wherein said growthfactors are one or more of a group consisting of FGF-2, FGF-5, IGF-1,TGF-β, BMP-2, BMP-7, PDGF, VEGF.
 24. A sterile cartilage defect repairmaterial as claimed in claim 21 wherein said bioabsorbable carrierconsists of sodium hyaluronate, hyaluronic acid and its derivatives. 25.A sterile cartilage defect material as claimed in claim 21 wherein saidlyophilized cartilage pieces have a water content ranging from about0.1% to 8.0%.
 26. A sterile cartilage defect implant material as claimedin claim 21 wherein said allograft articular cartilage is hyalinecartilage.
 27. A sterile allograft cartilage defect implant material asclaimed in claim 21 wherein said milled cartilage is fibrous cartilage.28. A sterile allograft cartilage defect implant material as claimed inclaim 21 wherein said milled cartilage is hyaline and fibrous cartilage.29. A sterile cartilage defect implant material as claimed in claim 21wherein said milled cartilage ranges from about 25% to about 50% byweight and said carrier ranges from about 75% to about 50% by weight.30. A sterile cartilage defect implant material as claimed in claim 21wherein said milled cartilage ranges from about 15% to about 30% byweight with the carrier ranging from about 85% to about 70% by weight.31. A sterile cartilage defect implant material comprising lyophilizedmilled allograft articular cartilage pieces ranging from 0.01 mm to 1.0mm in size in a bioabsorbable carrier taken from a group consisting ofsodium hyaluronate, hyaluronic acid and its derivatives, gelatin,collagen, chitosan, alginate, buffered PBS, Dextran or polymers andautologous stem cells in an amount exceeding the natural occurrence ofsame in a patient being treated.
 32. A method of placing a cartilagedefect material in a cartilage defect, said cartilage defect materialcomprising milled allograft articular cartilage which has beenlyophilized and mixed in a bioabsorbable carrier comprising the stepsof: (a) cutting a patient's tissue at a site of a cartilage defect toremove a diseased area of cartilage; (b) adding autologous cells to saidmixture of milled allograft cartilage in a bioabsorbable carrier; (c)placing a mixture of milled allograft cartilage with added autologouscells in a bioabsorbable carrier in the cartilage defect area wherecartilage has been removed; and (d) placing a cover over the mixture ofmilled allograft cartilage in a bioabsorbable carrier to contain themixture in cartilage defect site for a predetermined period of time. 33.The method of claim 32 wherein growth factors are added to said mixture.34. The method of claim 32 wherein said autologous cells arechondrocytes.
 35. The method of claim 32 wherein said autologous cellsare bone marrow cells.
 36. The method of claim 32 wherein saidautologous cells are stem cells.
 37. A sterile cartilage defect implantmaterial comprising lyophilized milled allograft articular cartilagepieces ranging from 0.01 mm to 1.0 mm in size in a bioabsorbable carriertaken from a group consisting of sodium hyaluronate, hyaluronic acid andits derivatives and chitosan and autologous chondrocytes in an amountexceeding the natural occurrence of same in articular cartilage, whereinsaid milled cartilage ranges from about 25% to about 50% by weight andsaid bioabsorbable carrier ranges from about 75% to about 50% by weight.38. A sterile cartilage defect implant material comprising lyophilizedmilled allograft articular cartilage pieces ranging from 0.01 mm to 1.0mm in size in a bioabsorbable carrier taken from a group consisting ofgelatin, collagen and alginate and autologous chondrocytes in an amountexceeding the natural occurrence of same in articular cartilage, whereinsaid milled cartilage ranges from about 25% to about 50% by weight andsaid bioabsorbable carrier ranges from about 75% to about 50% by weight.39. A sterile cartilage defect implant material comprising lyophilizedmilled allograft articular cartilage pieces ranging from 0.01 mm to 1.0mm in size in a bioabsorbable carrier taken from a group consisting ofbuffered PBS, Dextran or polymers and autologous chondrocytes in anamount exceeding the natural occurrence of same in articular cartilage,wherein said milled cartilage ranges from about 25% to about 50% byweight and said bioabsorbable carrier ranges from about 75% to about 50%by weight.